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Asembia 2025 

Topic

Sales and Marketing

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Leslie Sandberg Orne is the president and chief executive officer of Trinity Life Sciences.

A phased launch approach may ultimately be more sustainable and enable maximum market penetration and commercial success with less upfront investment than traditional “go-for-broke” strategies.

Strategies for Success in an Evolving Commercialization Landscape 

AbbVie Pedro Valencia ADCs

PE: How is AbbVie using novel cancer biomarkers to develop potential first-in-class ADCs for the treatment of advanced solid tumors?

We're constantly looking for biomarkers that can help us to do two key things. The first is to tackle cancer cells. and spare normal cells. We’re looking for specific antigens that are over-expressing tumor cells, and you see limited expression in normal cells. We want to make sure that target that’s over-expressed is critical for the survival of the cancer cell. Once you block it, you can actually drive a cancer cell death. That’s what we're looking for. In that perspective, c-Met is one of those biomarkers that is over expressing multiple tumor types such as lung, colorectal, gastric, and other GA tumors. We as an industry have tried to tackle c-Met in the past but have been unsuccessful. It would actually be successful to tackle what we call met, which is a gene inside the cell.

There’s this thing called met amplification, where the cancer cell produces multiple copies of the gene, and around 30% of patients have it. We can actually tackle that with small molecules. But once the gene becomes a protein and gets over-expressed in the cell, that over-expression is something we haven’t been able to target. For example, we know that on lung cancer, c-Met over-expression is about 25% to 50% in colorectal cancer, and it could be anywhere from 30% to 70% depending how you measure it, so it’s quite prevalent.

With ADCs, we’re trying to tackle c-Met over-expression on the surface of cancer cells. That was novel, and we can do it through ADCs. 706 has a target called SEZ6, and it’s a target that is over expressed in neuroendocrine cells or neuroendocrine neoplasms. When you think about it, multiple tumor types kind of have a subset of cells that are neuroendocrine driven. Small cell lung cancer is one of the few that has everything driven by neuroendocrine cells. The beauty of SEZ6 is over-expressing those cells and limited expression in normal cells. So, we can tackle it with an ADC and drive the results that we're seeing today.

PE: ADCs have redefined the treatment of cancer in recent years. Can you please discuss the promise of this emerging class and what the future may hold?

At the end of the day, ADCs work like a trojan horse. You have a good antibody that cancer cells are happy to receive, but once you hook into the cancer cell receptor, you deliver the payload, which is pretty much chemotherapy. It’s actually a highly potent version of the regular chemotherapy cancer patients are given on a regular basis. So, from that perspective, our goal is to replace chemotherapy. Our grand goal with ADCs is to replace good old, decades old chemotherapy that is really toxic for some patients. That’s how we see the redefinition of cancer treatment in the future with ADCs. So, what do we see in the future? Well, if you think about it, chemotherapy is being given in combination with other agents. In the future, we see ADCs being given in combination with chemotherapy. There will be one with other agents such as immuno-oncology agents. So, if you combine the ADC and the PD1s, you can start seeing that synergy come together and kind of start really dreaming about cures for the patients. All in all, we're super excited about ADCs replacing chemotherapy. 

In an interview with Pharm Exec Associate Editor Don Tracy, Pedro Valencia, VP, Solid Tumor Pipeline Strategy & Execution, AbbVie, discusses using novel cancer biomarkers to develop potential first-in-class antibody drug conjugates (ADCs) and the promise that they offer. 

Utilizing Biomarkers to Develop First-in-Class Antibody Drug Conjugates to Treat Advanced Solid Tumors

The FDA has issued a second complete response letter (CRL) to Regeneron’s odronextamab based on issues with a third-party manufacturing site purched by Novo Nordisk in December 2024, Catalent Indiana LLC, the company announced in its Q2 earnings report.

FDA Cites Third-Party Site Issues in CRL and Regulatory Delay

Regeneron’s Biologics License Application (BLA) is seeking the approval of odronextamab for the treatment of relapsed/refractory (R/R) follicular lymphoma (FL) and for R/R diffuse large B-cell lymphoma (DLBCL) following two or more prior lines of systemic therapy.

Regeneron also stated that it anticipates regulatory approvals to be delayed for a pending application for Eylea HD (aflibercept) injection 8 mg. The application, which was 

, seeks to expand use of the treatment for patients with macular edema following retinal vein occlusion to permit monthly dosing across all currently approved indications.

 The application was assigned PDUFA target action date of August 19, 2025.

Odronextamab’s Path to Approval Complicated by Evolving Phase III Trial Timelines

These delays are associated with issues raised during an FDA general site inspection at the Catalent Indiana LLC filler site, which was recently acquired by Novo Nordisk A/S. The inspection was completed in mid-July and was not specific to Eylea HD or odronextamab, according to Regeneron.

“Novo has been in communication with the FDA and expects to submit its response next week,” Regeneron stated in a press release. “Based on the Company's review of the observations and Novo's proposed response to the FDA, along with the progress the Company has made with alternate third-party fillers, the Company anticipates an expeditious resolution of the filling issues for Eylea HD.”

The first CRL issued to the BLA for odronextamab in March 2024 was based on the enrollment status of the confirmatory trials, but the FDA did not cite approvability issues related to the drug’s efficacy, safety, trial design, labeling, or manufacturing, according to Regeneron.

The FDA previously granted Priority Review to the BLA for odronextamab based on findings from the Phase 1 ELM-1 trial (NCT02290951) and the pivotal Phase II ELM-2 trial (NCT03888105).

“Regeneron has been actively enrolling patients in multiple Phase III trials for odronextamab as part of the OLYMPIA program—one of the largest clinical programs in lymphoma,” the company stated in a March 2024 press release. “As the OLYMPIA program is intended to change the treatment paradigm of several B-cell non-Hodgkin lymphoma subtypes—including in earlier lines of therapy—in agreeing to the program, the FDA required that the trials include both dose-finding and confirmatory portions. Enrollment in the dose-finding portion has begun, but the CRLs indicate that the confirmatory portions of these trials should be underway and that the timelines to completion be agreed prior to resubmission.”

Regeneron Posts Strong Q2 Earnings with Growth from Dupixent and Eylea HD US Sales

Despite these regulatory delays, Regeneron noted positive momentum across its lines of business. The company’s Q2 revenue increased 4% to $3.68 billion compared to the same period last year. This was powered by an increase in global net sales for Dupixent (dupilumab), which increased 22% to $4.34 billion. US net sales for Eylea HD increased 29% to $393 million; however, total Eylea HD and Eylea US net sales dropped 25% to $1.15 billion.

"Regeneron had a strong quarter, marked by significant growth in US sales of Eylea HD and global sales of Dupixent and Libtayo along with multiple regulatory approvals," Leonard S. Schleifer, MD, PhD, board co-chair, president and CEO of Regeneron, said in the release. "We have made significant progress in our oncology portfolio, including FDA approval for Lynozyfic for relapsed or refractory multiple myeloma, exciting emerging data from the lead-in cohorts of our pivotal programs in myeloma and lymphoma, as well as positive pivotal data supporting a potential upcoming FDA approval for Libtayo in adjuvant CSCC. 

"Dupixent continues to be the world-leading treatment for diseases driven by type 2 inflammation, adding recent FDA approvals for bullous pemphigoid and chronic spontaneous urticaria, the seventh and eighth distinct indications for this important medicine. We are confident in the near- and long-term potential of our diverse pipeline and look forward to additional data and regulatory milestones later this year."

1. Regeneron Reports Second Quarter 2025 Financial and Operating Results. News release. Regeneron. August 1, 2025. Accessed August 1, 2025. 

https://www.globenewswire.com/news-release/2025/08/01/3125690/0/en/Regeneron-Reports-Second-Quarter-2025-Financial-and-Operating-Results.html

2. EYLEA HD® (aflibercept) Injection 8 mg sBLA Accepted for FDA Priority Review for Both the Treatment of Macular Edema Following Retinal Vein Occlusion (RVO) and for Monthly Dosing in Approved Indications. Regeneron. April 17, 2025. Accessed August 1, 2025. 

https://investor.regeneron.com/news-releases/news-release-details/eylea-hdr-aflibercept-injection-8-mg-sbla-accepted-fda-priority

3. Regeneron Provides Update On Biologics License Application For Odronextamab. Regeneron. News release. March 25, 2024. Accessed August 1, 2025. 

https://investor.regeneron.com/news-releases/news-release-details/regeneron-provides-update-biologics-license-application

4. Odronextamab BLA for treatment of relapsed/refractory follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) accepted for FDA priority review. News release. Regeneron Pharmaceuticals. September 29, 2023. Accessed August 1, 2025. 

https://investor.regeneron.com/news-releases/news-release-details/odronextamab-bla-treatment-relapsedrefractory-follicular

Regeneron faces regulatory delays for odronextamab due to issues at a third-party manufacturing site, Catalent Indiana LLC. The FDA's second complete response letter (CRL) cites these site issues, impacting the approval timeline for odronextamab, intended for relapsed/refractory follicular lymphoma and diffuse large B-cell lymphoma. Despite these setbacks, Regeneron reports strong Q2 earnings, driven by increased sales of Dupixent and Eylea HD. The company remains optimistic about its oncology portfolio and anticipates resolving the manufacturing issues swiftly to continue its progress in clinical trials.

Regeneron has received a second complete response letter from the FDA for odronextamab and anticipates delays for Eylea HD due to inspection findings at a Novo Nordisk-owned manufacturing site, despite continued strong revenue growth and pipeline momentum.

Regeneron Faces FDA Setbacks with CRL for Odronextamab, Delays on Eylea HD BLA Amid Third-Party Manufacturing Issues

In the rapidly evolving world of healthcare marketing, one of the biggest challenges that marketers face is reaching and engaging healthcare professionals (HCPs) effectively.

 To overcome this issue, pharma brands have traditionally promoted their products by drawing up partnerships with individual medical journals. However, this strategy hasn’t always yielded great benefits.
In fact, this approach has increasingly proven to be inadequate in delivering the scale, efficiency, and precision required to meet modern marketing goals. In the current context, to enhance HCP reach and engagement, brands must invest in more flexible, smarter and more scalable strategies. Instead of direct partnerships, it’s time they make the switch to solutions that maximize impact through scale, streamlined operations, and advanced targeting capabilities.

The Limitations of Single/Direct Partnership: Capped Reach and Scale

One of the most significant drawbacks for a brand when partnering with individual medical journal platforms is the limitation in reach and scalability they possess. While individual medical journal platforms are a good way to reach niche audiences, because of their nature they only cater to a select crowd of HCPs across limited geographies. This often proves to be a major bottleneck that pushes brands to forge multiple partnerships––each tailored to achieve a specific purpose and reach specific audience segments. In practice, this ultimately ends up creating a fragmented strategy that is extremely difficult to maintain in optimal shape in the long run, leading glaring gaps in HCP coverage and engagement.

The scalability of marketing activities is another major pain point for brands going ahead with such fragmented strategies. Due to the many partners involved in the picture and multiple moving parts because of it, it becomes difficult for brands to scale up their campaigns or for the matter make alterations mid campaign. This is because each new partnership requires fresh negotiations, integrations, and campaign adaptations, making it difficult for brands to streamline processes leading to lower returns on investment. Additionally, the fragmented nature of direct partnerships bottlenecks the potential audience size, making it nearly impossible to engage HCPs at scale.

Solutions that offer support for integrated medical journal publishers stand out as compelling alternatives. Depending on the size of the platform and the partnerships it brings under its umbrella, it can aggregate varied audiences from across a portfolio of medical journals providing access to a diverse and expansive HCP population through a single point of contact. By turning towards such integrated solutions, brands can tap into a pre-existing, broad audience base without the need to manage multiple partnerships. This consolidated approach ensures greater reach without very little fuss.

Resource-Intensive Management: The Hidden Costs of Fragmentation

Beyond the scope of their reach, another disadvantage that brands face when it comes to direct partnerships is the fact that they are extremely resource intensive. This is because under such a partnership, each platform requires dedicated time and effort for even hygiene tasks, let alone slightly complex ones such as contract negotiations, creative approvals, campaign execution, and performance tracking.

Moreover, partnering with individual medical journal platforms can also lead to tackling their unique requirements that spread over multiple partnerships can complicate campaign management. As such for a brand working with multiple medical journal platforms such partnerships could translates into a logistical nightmare.

Solutions that offer an integrated publisher management system do not run into such troubles as they offer a unified interface for campaign execution. So instead of negotiating with multiple publishers, brands can work with a single platform to roll-out campaigns. The major benefit of this in the streamlining of operations which then reduces the need for extensive coordination and allowing teams to focus on strategy and innovation instead.

Such platforms also bring reporting and analytics under one umbrella, thus helping brands to easily and effectively monitor performance across channels. Additionally, by consolidating data from multiple publishers under one platform, brands can easily track what’s working for them and what’s not -- something that also helps them course correct on the fly.

Inefficient Targeting and Personalization

Individual medical journal platforms also face issues when it comes to audience targeting as well as personalizing and contextualizing messaging. This is because individual platforms often lack access to infrastructure that can help them collect rich data––needed to deliver highly targeted campaigns. As a result, their targeting lacks precision, which in turn reduces relevance, leading to lower engagement rates and wasted messaging spends.

The lack of deep data insights also puts such individual platforms at a disadvantage when it comes to personalization of their messaging attempts. This often proves to a limiting factor as HCPs expect content that speaks directly to their needs. However, as many individual platforms lack the ability to tailor content based on individual preferences or behaviors, brands struggle to deliver the right message to the right HCP at the right time, diminishing the impact of their campaigns.

Through integrated publisher platforms such challenges can be addressed as these platforms offer access to rich data that can be used for enhancing HCP targeting. Moreover, an ideal solution that brings under its umbrella multiple medical journal platforms should also be able to leverage the power of artificial intelligence (AI) and machine learning to enhance personalization and contextual relevance. The effective use of technology can be used improve content delivery in real time, ensuring that HCPs receive the most relevant information based on their current interests or browsing behavior, thus ensuring brands can move beyond static, one-size-fits-all campaigns to dynamic, contextually aware strategies that deliver measurable results. Case in point, this report from The Institute of Data

 which attributes a 5.3x rise in click-through rates when brands use targeted ads.

The Case for Integrated Publishers: Scale, Efficiency, and Impact

The healthcare marketing industry is witnessing a paradigm shift with brands moving to integrated solutions with access to multiple medical journal platforms. Through this, they are exploring the benefits of improved scale and reach without adding a layer of complexity to their campaigns when it comes to managing them.

They are enjoying the benefits of streamlined operations offered by integrated publishers that reduce administrative burdens, allowing teams to allocate resources more effectively and focus on strategic priorities. Over and above these, brands and their marketing partners are enjoying the benefits that AI and ML-based solutions bring in terms of significantly improving targeting and personalization of messaging.

Suffice to say, the era of platform-by-platform promotion is giving way to a more strategic, scalable approach to HCP engagement. Integrated medical journal publishers are emerging as a viable solution for brands seeking to amplify their reach, streamline operations, and deliver highly targeted, impactful campaigns.

The Biggest Challenges (and Solutions) in Healthcare Marketing. 

https://www.pdqcom.com/blog/biggest-healthcare-marketing-challenges-solutions

Harnessing Strategic HCP Segmentation for Pharma Success. 

https://viseven.com/hcp-audience-segmentation-omnichannel-pharma-strategy/

Healthcare marketing is evolving, with traditional partnerships with individual medical journals proving inadequate for reaching and engaging healthcare professionals (HCPs) effectively. These partnerships often result in limited reach, scalability issues, and resource-intensive management. Integrated publisher platforms offer a solution by aggregating diverse audiences, streamlining operations, and enhancing targeting and personalization through advanced data analytics and AI. This shift allows brands to achieve greater scale, efficiency, and impact in their campaigns, moving away from fragmented strategies to more strategic, scalable approaches for HCP engagement.

One of the most significant drawbacks for a brand when partnering with individual medical journal platforms is the limitation in reach and scalability they possess.

From Scatter to Scale: Rethinking Marketing/Programmatic Strategy for Amplified HCP Reach and Engagement

For decades, modern pharmacology has pursued a singular goal: to isolate the active ingredient, refine it, and set aside the supporting compounds once considered irrelevant. This model has brought us extraordinary therapies. But when it is the only model, it limits how we treat patients and their unique conditions. Some conditions are too complex for a single compound to fix. And some therapeutic effects come not from isolation of a molecule, but from the collaboration of many.

This is the promise of botanical drugs: a new class of clinically validated therapies that benefit from the full spectrum of a plant’s chemistry while meeting the highest scientific and regulatory standards of modern drug development.

Unlike traditional single-molecule drugs derived from plants, such as morphine or Epidiolex, botanical drugs preserve the complex web of compounds in their source material. This complexity is unique to botanical medicine, as it involves multiple compounds that work together to enhance absorption, balance psychoactivity, or broaden therapeutic effects. This is known as the Entourage Effect.

The term was first coined by the late Raphael Mechoulam, widely regarded as the godfather of cannabinoid science. He and his colleagues observed that cannabinoids like THC acted differently, and often more effectively, when in the presence of other naturally occurring compounds such as CBD, CBG, and terpenes like myrcene. “A single molecule, a single compound from cannabis, is not as effective as the whole plant,” Mechoulam noted. This insight helped shift the paradigm from isolating compounds toward understanding how cannabinoids work in a synergistic system– a principle now central to botanical drug development.

But this isn’t unique to cannabis. It appears to extend to psychoactive mushrooms, where naturally occurring compounds like psilocin, baeocystin, norbaeocystin, and aeruginascin may work together to produce more potent and sustained therapeutic outcomes than synthetic psilocybin alone. Research shows that full-spectrum mushroom extracts can have a stronger and longer-lasting effect on synaptic plasticity, suggesting the Entourage Effect may be at play in fungi as well.

The principle likely extends even further, to plants that we haven’t had the technology to examine in this way until now. In many plants, the full expression of therapeutic value only emerges when their components are allowed to work in concert.

Science is catching up to what nature has consistently demonstrated: systems respond to systems. Humans are not simple machines but complex biological ecosystems, with countless cell receptor sites capable of interacting with multiple molecules at once. For most of human history, our bodies evolved alongside plants, interfacing with their compounds in whole, synergistic form. It’s only in the last century, driven by pharmaceutical convenience, that we began isolating and concentrating single molecules. While that has brought life-saving advances, it has also introduced a new era of side effects, tolerances, and unintended consequences. It is in our DNA to interact with the full spectrum of nature’s chemistry– and many patients are instinctively returning to that interface. That’s why many patients with complex, chronic, neurodevelopmental, or multifactorial conditions are turning to botanical options, sometimes without formal guidance, to find what conventional drugs have not yet delivered.

We now have the technology to meet this complexity with precision. Analytical chemistry, biomanufacturing, and stringent quality controls enable the mapping, measurement, and standardization of the full chemical fingerprint of a plant-based therapeutic. This is what the FDA requires for botanical drug approval: evidence, consistency, and repeatability.

In this way, a botanical drug is not a supplement with better packaging. It is a pharmaceutical, developed within a rigorous regulatory framework. But it is also a mindset shift that sees complexity as a therapeutic advantage rather than something too complex to standardize.

This entry comes at a time when patient demand is accelerating. The global botanical drug market, valued at $37.5B in 2024, is projected to reach over $58B by 2033. In the U.S., the market is expected to grow more than 10% annually. This is a more profound shift in what patients want from medicine: not just control over symptoms, but collaboration with the body’s systems.

The pharmaceutical playbook has been focused on disrupting pathways with isolated, novel compounds. But healing often requires restoring balance. Ironically, it may be multi-compound natural drugs, with foundations in ancient use, that now disrupt the entrenched norm of single-target molecules and their side effects. Botanical drugs open the door to that possibility. They offer a path to serve conditions where conventional approaches have fallen short, and to do so with credibility, safety, and evidence.

We don’t have to choose between nature and science. We need both. And now, for the first time, we have a regulatory and technological path to achieve this goal.

Modern pharmacology's focus on isolating active ingredients has led to significant therapeutic advancements but limits treatment for complex conditions. Botanical drugs, preserving the full spectrum of plant chemistry, offer a promising alternative by leveraging the Entourage Effect, where multiple compounds work synergistically. This approach is gaining traction, particularly for conditions where conventional drugs fall short. With advancements in analytical chemistry and regulatory frameworks, botanical drugs are poised to disrupt traditional pharmaceutical models, offering a balanced, evidence-based approach that aligns with the body's natural systems.

In many plants, the full expression of therapeutic value only emerges when their components are allowed to work in concert.

How the Entourage Effect Is Reshaping Botanical Drug Development

No biopharma company wants to receive a complete response letter (CRL) on a drug that has taken years to test and major cash to develop—let alone a CRL an executive did not expect.

That’s what happened to Replimune Group, Inc., on July 22, when the FDA issued a CRL for the company’s advanced melanoma treatment, RP1. The move surprised the company, which said none of the issues raised in the CRL were addressed in mid- and late-cycle reviews.

The decision also surprised Wall Street analysts and investors. The news dropped before the market opened on July 22, and the company’s stock proceeded to plunge nearly 77%, from about $13-a-share to around $3-a-share. Prior to the news, the investors expected RP1 to be approved on accelerated approval pathway and described the rejection as a surprise.

A similar but perhaps less dramatic story played out earlier in July, when Capricor Therapeutics, Inc. received a CRL for its investigational Duchenne muscular dystrophy therapy, citing outstanding items in the chemistry, manufacturing, and controls part of the application, which the company claimed it had already addressed.

Both organizations have since requested Type A meetings with FDA officials to discuss their paths forward.

Replimune and Capricor are individual situations but, taken together, they raise new questions for both the biopharmaceutical industry and investors alike. Pharma and biotech obviously rely on FDA approval, and these recent announcements have many people wondering what to expect next. How will these changes impact investors and how pharma companies communicate with them? More importantly, how can industry and investors adjust their strategies for these new rules?

How can pharma companies prepare and strategize based on recent unexpected FDA decisions?

One factor is that leadership at the FDA has changed since Replimune submitted its BLA under the accelerated approval pathway in November 2024. Many senior regulators have left or been forced out as part of a leadership and staff shakeup. Meanwhile, the agency has also pushed transparency, recently publishing hundreds of CRLs from past years, although only those for drugs that were ultimately approved.

So now biopharma companies with drugs in the review process and an approaching PDUFA date are wondering: Will we be next?

"This decision at the end of the process is difficult,” said Replimune CEO Sushil Patel , Ph.D., in a July 23 interview with BiotechTV. “I do think it’s going to make it extremely difficult for small companies such as us—investors also—to have trust that they are going to put money into companies with innovative products, if they feel that things could change late in the process. ... There's also patients waiting at the end of the day."

It’s a challenging time for drug developers because of this uncertainty, especially those that based their development strategies and investments on the communications they had with FDA officials from the prior administration, said Craig Lipset, co-chair, Decentralized Trials & Research Alliance, in an email interview with 

“It raises questions for developers today as to whether past understandings still hold true, as well as the potential risks and benefits of re-engaging with FDA on active development programs based on those past agreements,” Lipset said.

The CRL to Replimune’s oncolytic immunotherapy candidate, RP1, did more than derail a priority review. It jolted investors and sparked questions about how the agency is communicating expectations. The timeline below tracks the pivotal regulatory and market moments that led to and followed the CRL.

For biopharma leaders, it’s a case study in why planning for multiple regulatory scenarios has never been more critical. Here’s a timeline of events:

: Replimune announces it has submitted its biologics license application (BLA) for RP1 under the accelerated approval pathway and that the FDA has granted Breakthrough Therapy designation for RP1 plus nivolumab in anti–PD-1–failed advanced melanoma.

: FDA accepts the BLA and grants Priority Review, setting a PDUFA action date of 

; FDA says no advisory committee is planned and no review issues are identified at that time.

 Replimune reiterates Priority Review status and the July 22 PDUFA date in its quarterly report.

 Vinay Prasad, MD, a hematologist oncologist, is named new lead for the FDA’s Center for Biologics Evaluation and Research.

: Investor optimism grows; Replimune shares rise about 32% in the weeks leading up to the decision.

: Replimune publicly discloses the CRL; press release states FDA found IGNYTE was “not an adequate and well-controlled” study and could not be “adequately interpreted” due to patient heterogeneity. Replimune CEO Sushil Patel, PhD, responded: “The issues highlighted in the CRL were not raised by the agency during the mid- and late-cycle reviews. Additionally, we had also aligned on the design of the confirmatory study.” The company stock plunged up to 77%, triggering multiple trading halts; shares ultimately fell below $3. Replimune requested a Type A meeting with FDA within 30 days to discuss the path forward.

Federal agency priorities always change when new presidential administrations take over, and in 2025, many high-profile regulators left or were forced out.

One of those high-profile officials who left was Peter Marks, MD, the former head of FDA’s Center for Biologics Evaluation and Research (CBER). His replacement is Vinay Prasad, MD.

When Prasad’s appointment was announced in early May, the biotech industry held its breath, because it indicated a tougher road ahead for cancer and rare disease developers. In past comments and writings, Prasad argued the FDA leaned too heavily on surrogate endpoints that don’t extend lives meaningfully and that drugs often cost too much for marginal benefit. His scholarship called for “more convincing clinical evidence.” His appointment immediately rattled markets, sending shares of cell and gene therapy companies sharply lower.

When the Replimune CRL was released, Wall Street observers believed that Prasad’s leadership of CBER was a factor in the surprise decision. According to a report published in 

analysts said Prasad likely played a “key role” in the decision.

Another factor in the changing world of FDA reviews to note is that in the event a biopharma company’ receives a CRL, it will probably go public.

Just prior to the Replimune announcement, the FDA revealed plans to publish CRLs as part of an initiative to embrace “radical transparency.” The agency published over 200 CRLs from 2020 to 2024, and FDA Commissioner Martin Makary, MD touted the initiative as a chance to provide clarity and predictability. for drug developers and capital markets.

“Today we’re one step closer to delivering it to them, with an ultimate goal of bringing cures and meaningful treatments to patients faster,” he said.

For now, questions remain on what impact the transparency initiative will have going forward, said Monica Gorman, currently the managing director at Crowell Global Advisors in Washington, DC, in an interview with 

 The CRLs that were published were older, and questions remain about what it means to publish them in real time, including for drugs that ultimately are not approved.

“There are very practical questions,” said Gorman, who is also former special assistant to the president for manufacturing and industrial policy and co-chair of the White House Supply Chain Disruptions Task Force. “Are there enough people to do the redactions? Obviously, the industry is going to have a lot of questions about confidential business information, trade secrets, and how all of that is going to be redacted. It’s difficult to know how the industry is going to respond from an investment standpoint until everyone has a better sense of what this actually means.”

Harpreet Singh, MD, former FDA division director of oncology and current chief medical officer at Precision for Medicine, called the move to make CRLs public a step toward greater transparency.

“It’s a testament to the agency’s evolving commitment to data sharing,” she said in an interview with 

. “Making these letters public can help demystify regulatory decision-making and offer sponsors and investors valuable insights. That said, the current approach focuses only on CRLs for drugs that were ultimately approved, leaving out many instructive examples tied to programs that didn’t advance. Having issued CRLs during my time at the agency, I’ve seen how these letters can bring value to sponsors by guiding development strategy, and broader disclosure could further their impact.”

While other have praised transparency as a positive, there’s another issue that needs to be considered: what impact the negative publicity of a CRL can have on a small biotech with a promising therapy clawing towards launch.

While CRLs are not a death sentence for a product and it’s entirely possible for a company to recover, timing is a major issue. Pharma companies and drug developers already have long timelines from development to launch. While many in the industry are calling for that timeline to be sped up, the FDA seems to be making moves to slow things down.

For companies that are getting good news, the slowdown is still frustrating. For a company receiving a CRL, it could be devastating.

A deep dive into the implications of the Replimune CRL that surprised insiders and investors, the role of new leadership at FDA’s CBER, and how industry can navigate the path forward.

Leslie Sandberg Orne

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